title: Cell susceptibility to baculovirus transduction and echovirus infection is modified by protein kinase C phosphorylation and vimentin organization.
abstract: Some cell types are more susceptible to viral gene transfer or virus infection than others, irrespective of the number of viral receptors or virus binding efficacy on their surfaces. In order to characterize the cell-line-specific features contributing to efficient virus entry, we studied two cell lines (Ea.hy926 and MG-63) that are nearly nonpermissive to insect-specific baculovirus (BV) and the human enterovirus echovirus 1 (EV1) and compared their characteristics with those of a highly permissive (HepG2) cell line. All the cell lines contained high levels of viral receptors on their surfaces, and virus binding was shown to be efficient. However, in nonpermissive cells, BV and its receptor, syndecan 1, were unable to internalize in the cells and formed large aggregates near the cell surface. Accordingly, EV1 had a low infection rate in nonpermissive cells but was still able to internalize the cells, suggesting that the postinternalization step of the virus was impaired. The nonpermissive and permissive cell lines showed differential expression of syntenin, filamentous actin, vimentin, and phosphorylated protein kinase C subtype α (pPKCα). The nonpermissive nature of the cells could be modulated by the choice of culture medium. RPMI medium could partially rescue infection/transduction and concomitantly showed lower syntenin expression, a modified vimentin network, and altered activities of PKC subtypes PKCα and PKCε. The observed changes in PKCα and PKCε activation caused alterations in the vimentin organization, leading to efficient BV transduction and EV1 infection. This study identifies PKCα, PKCε, and vimentin as key factors affecting efficient infection and transduction by EV1 and BV, respectively.
authors.affiliation: Department of Biological and Environmental Science, Division of Cell and Molecular Biology-Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Turkki
authors.forename: Kaisa-Emilia
authors.initials: KE
authors.lastname: Makkonen
authors.forename: Moona
authors.initials: M
authors.lastname: Huttunen
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Laakkonen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Airenne
authors.forename: Varpu
authors.initials: V
authors.lastname: Marjomäki
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D002460:Cell Line; D003470:Culture Media; D029822:Enterovirus B, Human / Q000472:pathogenicity* / Q000502:physiology; D057809:HEK293 Cells; D056945:Hep G2 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism; D014161:Transduction, Genetic; D014746:Vimentin / Q000378:metabolism*; D014774:Virulence; D053586:Virus Internalization
chemical_list: D003470:Culture Media; D038982:Integrin alpha2beta1; D011991:Receptors, Virus; C508241:SDC1 protein, human; D053668:Syndecan-1; D014746:Vimentin; C496628:PRKCA protein, human; C497255:PRKCE protein, human; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon